Preferential binding and structural distortion by Fe2+ at RGGG-containing DNA sequences correlates with enhanced oxidative cleavage at such sequences.
Preferential binding and structural distortion by Fe2+ at RGGG-containing DNA sequences correlates with enhanced oxidative cleavage at such sequences.
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DOI：
10.1093/nar/gki192
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发表时间：
2005
影响因子：
14.9
通讯作者：
Linn S
中科院分区：
文献类型：
--
作者：
Rai P;Wemmer DE;Linn S
已知某些DNA序列对经由Fe 2+介导的芬顿反应的切口异常敏感。最值得注意的是嘌呤核苷酸后接三个或更多个G残基，RGGG，以及侧翼为TG组合的嘌呤核苷酸，RTGR。我们的实验室以前证明，在RGGG序列中的切口优先发生在5′端到G残基，切口概率从这些序列的5′端到3′端逐渐降低。用1H NMR表征了Fe 2+在双链体CGAGTTAGGGTAGC/GCTACCCTAACTCG及其含7-脱氮鸟嘌呤（Z）的变体中的结合，我们表明Fe 2+优先结合在GGG序列，最强烈地朝向其5′端。用Z取代单个鸟嘌呤表明，在AGGG处的高亲和力Fe 2+结合涉及两个相邻的鸟嘌呤N7部分。结合伴随着特定亚氨基、芳香族和甲基质子化学位移的巨大变化，表明在结合位点形成了局部扭曲的结构，影响了GGG序列3′端两个碱基对的构象。Fe 2+与RGGG的结合与先前观察到的RTGR序列形成对比，RTGR序列以可忽略的结构重排结合Fe 2+。
Certain DNA sequences are known to be unusually sensitive to nicking via the Fe2+-mediated Fenton reaction. Most notable are a purine nucleotide followed by three or more G residues, RGGG, and purine nucleotides flanking a TG combination, RTGR. Our laboratory previously demonstrated that nicking in the RGGG sequences occurs preferentially 5′ to a G residue with the nicking probability decreasing from the 5′ to 3′end of these sequences. Using 1H NMR to characterize Fe2+ binding within the duplex CGAGTTAGGGTAGC/GCTACCCTAACTCG and 7-deazaguanine-containing (Z) variants of it, we show that Fe2+ binds preferentially at the GGG sequence, most strongly towards its 5′ end. Substitutions of individual guanines with Z indicate that the high affinity Fe2+ binding at AGGG involves two adjacent guanine N7 moieties. Binding is accompanied by large changes in specific imino, aromatic and methyl proton chemical shifts, indicating that a locally distorted structure forms at the binding site that affects the conformation of the two base pairs 3′ to the GGG sequence. The binding of Fe2+ to RGGG contrasts with that previously observed for the RTGR sequence, which binds Fe2+ with negligible structural rearrangements.
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